Behavioral deficits of alcoholics have been conceptualized in terms of two neuropathologically distinct syndromes: alcoholic dementia and korsakoff's psychosis (alcohol amnestic disorder). Alcoholic dementia is characterized by diffuse cortical damage primarily related to the neurotoxicity of alcohol; Korsakoff's psychosis is associated with subcortical lesions due to nutritional (thiamine) deficiency. Severe memory impairment with relative sparing of other intellectual functions distinguishes Korsakoff's psychosis from alcoholic dementia (which may be clinically indistinguishable from the most common cause of dementia, Alzheimer's disease). We have recently found that sleep in volunteers, whereas Alzheimer patients have normal latencies. Furthermore, delta sleep is reduced in Alzheimer's disease, but is normal in Korsakoff patients. We have also demonstrated reduced daily excretion of the major urinary metabolite of melatonin, hydroxymelatonin, in patients with Korsakoff's psychosis. This finding is suggestive of impaired pineal function. Genetic differences in thiamine metabolism may predispose patients to develop Korsakoff's psychosis. Most patients with Korsakoff's psychosis whom we have studied have had a transketolase with reduced affinity for thiamine pyrosphosphate. The majority of alcoholics with cognitive impairment demonstrate features characteristic of both syndromes. Pharmacologic modulation of neurotransmitter systems may be effective in treatment of the subcortical syndrome, whereas alcoholic dementia may require treatment strategies similar to those in Alzheimer's disease. This protocol is intended to utilize clinical, neuroradiological, physiological, and neuropharmacological tests to differentiate these two pathologic entities, to follow a longitudinal course, and to relate variables in treatment protocols to outcome.